Comparative studies on the intestinal flora found in breast-fed infants and that in bottle-fed infants have suggested that bifidobacteria are useful for improving human health. As has been confirmed, the amount of bifidobacteria in the body is significantly reduced by gastrointestinal tract diseases or similar diseases, or aging, and promotion of proliferation of intestinal bifidobacteria is effective for preventing carcinogenesis, intestinal putrefaction, infectious diseases, and other health problems. Therefore, selective proliferation of intestinal bifidobacteria is considered very important for maintaining health and preventing and treating various diseases, including life-style-related diseases.
Conventionally, several substances capable of promoting proliferation of useful bifidobacteria—such a substance is called a “Bifidus factor”—have been studied and reported. Examples of the substances include N-acetylglucosamine, which is found in breast milk (Proc. Soc. Exp. Biol. Med., 90, 219 (1955)); peptide-related substances (Am. J. Clin. Nutr., 32, 1428 (1979) and Agric. Biol. Chem., 48, 2159 (1984)); carrot extracts (Journal of Japan Society for Bioscience, Biotechnology, and Agrochemistry, 55, 499 (1981) and Chem. Pharm. Bull., (Tokyo) 14, 1191 (1966)); and sugar-related substances (Proceedings of Tohoku Fukushi University, 10, 313 (1986)).
However, preparation of any of these substances capable of promoting proliferation of bifidobacteria requires an intricate process, and the effect of such substances in terms of selective proliferation of merely bifidobacteria needs to be improved.
In view of the foregoing, the present inventors have performed extensive studies on compounds capable of selectively promoting proliferation of bifidobacteria, and as a result have found that certain types of naphthoquinone derivatives and naphthalene derivatives exhibit strong activity in promoting proliferation of various bifidobacteria (e.g., Bifidobacterium longum, B. breve, B. adolescentis, B. bifidum, B. infantis, B. animalis, and B. pseudolongum). Also, the present inventors have disclosed, in addition to these known compounds, a highly active bifidobacteria proliferation promotion substance, and have confirmed that this substance is 2-amino-3-carboxy-1,4-naphthoquinone, which is a conventionally unknown (in other words, novel) substance, and is produced intracellularly and extracellularly by a bacterium belonging to the genus Propionibacterium (Japanese Patent Application Laid-Open (kokai) No. 8-98677). Furthermore, the present inventors have found that 2-amino-3-carboxy-1,4-naphthoquinone is useful as a drug for preventing or treating metabolic bone diseases such as osteoporosis (WO 01/28547).
Meanwhile, DHNA has been known to be useful as an industrial material such as a dye, a pigment, or a photosensitive material, and various organic chemical synthetic methods for DHNA have been developed (e.g., Japanese Patent Application Laid-Open (kokai) Nos. 57-128655, 59-186942, and 60-104037). However, such a conventional synthetic method requires high-temperature, high-pressure reaction in an organic solvent, or employment of, for example, an inedible reagent as a catalyst or the like. In addition, difficulty is encountered in completely removing, from DHNA produced through such a method, solvents or reagents employed for production thereof. Therefore, DHNA produced through such a conventional production method has not been considered to be useful in foods and beverages or in drugs.